The indispensable amino acid histidine plays an important role as a precursor of carnosine and of histamine. The former compound has been implicated as a possible neurotransmitter in the primary olfactory pathway while the latter has been shown to be important in reaction to physiological stress (wound repair, infection, granulation, vasodilation). We propose to study the role of histidine dipeptides in response to trauma and in relation to olfactory ability. Regarding olfaction, we will attempt to establish the physiological significance of carnosine the olfactory bulb, vis-a-vis a neurotransmitter at the first synapse in the olfactory bulb. We will then alter the dietary histidine intake and use a histidine analogue, 2-fluorohistidine, to prevent formation of biologically active carnosine or to act as an antagonist of carnosine binding at the postsynaptic receptor of the carnosinergic neurons in the olfactory bulb. A second aspect of these studies will be to investigate the histamine precursor roles of muscle carnosine and anserine in relation to trauma (ether anesthesia plus back skin incisions), superimposed upon rats fed graded levels of histidine. We believe that muscle carnosine may act as a histidine reservoir for increased histamine utilization during periods of stress. In this regard, we will inject various imidazole-containing compounds near the localized site of trauma in rats which have been fed graded levels of histidine (and therefore will have graded levels of muscle carnosine concentration) in order to clarify the metabolic relationships among histidine, muscle carnosine and anserine, and histamine concentrations including the enzymes that form it (histidine decarboxylase) and that catabolize it (histamine methyl transferase) during the physiological response to trauma.